The specific objective of this research proposal is to employ biochemical and freeze-fracture techniques to identify which catecholamines are involved in the transduction of chemoreceptor information and then to identify which of the synaptic sites between the various components of the carotid body are active during stimulation. In these studies the levels of dopamine (DA) and norepinephrine (NE) will be measured in carotid bodies excised from live ventilated rats and changes in the levels of these amines compared during normoxia, hypoxia and hypercapnia. A sensitive radioisotope-enzyme procedure will be employed to quantify the content and the turnover of DA and NE in the carotid body. Additionally, the synaptic active zones between the glomus cells and the afferent nerve endings and between adjacent glomus cells will be studied during normoxia and under hypoxic stimulation using the freeze-fracture technique. Various characteristic parameters of the morphology of the presynaptic membrane indicative of synaptic activity will be assessed using stereological techniques to determine which cellular components of the carotid body are involved in communication with one another. Thin section electron microscopy also will be employed to correlate the data gathered from the freeze-fracture replicas. Evidence obtained from these experiments will be correlated with two widely accepted hypotheses of chemoreceptor function. An understanding of the basic mechanisms involved in chemoreceptor function may help us to better understand the carotid body abnormalities associated with sudden infant death syndrome or how chemoreceptors initiate and maintain hyperventilation during various cardiovascular disease states.